Study first to examine how early memory changes as we age at a cellular level

Newswise — How do our brains acquire the ability to form distinct memories? In an initial investigation on memory formation during adolescence, a group of researchers at The Hospital for Sick Children (SickKids) potentially pinpointed a molecular factor behind memory alterations during early stages of life.

Event-based memories, commonly referred to as episodic memories, are the conventional perception of memories, where recollections are associated with specific contexts. Nevertheless, in the case of young children, memory tends to be more broad and akin to a general or "gist" representation, lacking specific contextual associations.

In a Science publication spearheaded by Drs. Paul Frankland and Sheena Josselyn, esteemed Senior Scientists within the Neurosciences & Mental Health program at SickKids, a study unveiled the molecular processes that drive the transition from generalized, gist-like memory to episodic memory in mice. The research team highlights the significance of comprehending this transition, which commonly takes place in children between the ages of four and six, as it can offer fresh perspectives in child development research and shed light on conditions impacting the brain, ranging from autism spectrum disorder to concussion.

"For decades, researchers have delved into the development of episodic memory, but the recent advancements in precise cellular interventions have finally allowed us to explore this question at the molecular level," explains Frankland, who additionally occupies a Canada Research Chair in Cognitive Neurobiology.

Growth of perineuronal net may trigger change in memory 

In the case of adults, memory traces, often referred to as engrams, consist of approximately 10 to 20 percent of neurons. However, in young children, the size of these engrams is notably larger, with approximately 20 to 40 percent of neurons constituting an engram that supports a memory.

What causes this change? The alteration can be attributed to the role of the hippocampus, a brain region involved in learning and memory. Within the hippocampus, there are various types of neurons, including a specific type of inhibitory cell called parvalbumin-expressing (PV) interneuron. These inhibitory cells play a crucial role in limiting the size of engrams and facilitating memory specificity. The research team discovered that as these interneurons mature, the transition from general to more specific memory occurs, and engrams form at the appropriate size.

Employing viral gene transfer technology pioneered by Dr. Alexander Dityatev, who leads the Molecular Neuroplasticity research group at the German Center for Neurodegenerative Diseases, the research team embarked on a deeper investigation to uncover the underlying cause of this change. Their findings revealed that the development of a dense extracellular matrix called the perineuronal net around these interneurons in the hippocampus is instrumental in the maturation process. This maturation subsequently alters the mechanisms by which our brains form engrams and store memories.

"After recognizing the crucial role of the perineuronal net in the maturation of interneurons, we were able to expedite the development of the net and induce the formation of specific episodic memories in juvenile mice, rather than general ones," explains Josselyn, who occupies a Canada Research Chair in Circuit Basis of Memory.

Informing new insights into brain function and cognition 

Although the research team successfully induced a change in memory type by accelerating the development of the perineuronal net, they emphasize that the underlying reasons for the age disparity between gist-like and episodic memories should not be disregarded. While their findings shed light on the molecular mechanisms involved, further investigation is necessary to fully comprehend the factors contributing to the chronological variation in memory types.

Adam Ramsaran, a PhD candidate in the Frankland Lab and the study's lead author, highlights the rationale behind the divergent functioning of memory in children compared to adults. "Considering the purpose memory serves, it is logical that a child's memory operates differently from that of an adult," Ramsaran explains. "At the age of three, it is unnecessary to recall specific details. A gist-like memory aids children in establishing a broad knowledge foundation, which can subsequently become more specific as they mature and accumulate more life experiences."

Expanding upon their molecular findings, the research team facilitated the accelerated growth of the perineuronal net by exposing subjects to an enriched environment. This manipulation facilitated the formation of specific memories. This groundbreaking discovery is now playing a significant role in advancing child development research being conducted at SickKids and the University of Toronto, opening up new avenues of exploration and understanding.

"Beyond memory development, we have also observed comparable mechanisms of maturation in various sensory systems within the brain," notes Frankland. "It appears that multiple brain regions utilize the same mechanism for different purposes, presenting intriguing possibilities for research and collaborative endeavors." This discovery paves the way for exciting opportunities to explore and deepen our understanding of the brain's intricate workings in different contexts and sensory domains.

This study was funded by Brain Canada, the Canadian Institutes of Health Research (CIHR), University of Toronto, SickKids Research Institute, German Research Foundation, German Center for Neurodegenerative Diseases, National Institutes of Health (NIH), Natural Sciences and Engineering Research Council of Canada (NSERC), Ontario Graduate Scholarship program, Ontario Trillium Scholarship program and the Vector Institute.